mu-Opioid peptides inhibit thalamic neurons.
Opioidergic inhibition of neurons in the centrolateral nucleus of the thalamus was investigated using an in vitro thalamic slice preparation from young rats. The mu-opioid receptor agonist D-Ala2,N-Me-Phe4,glycinol5-enkephalin (DAMGO) evoked a hyperpolarization and decrease in input resistance that was reversible, concentration-dependent, and persisted in the presence of tetrodotoxin. Application of the specific mu-receptor antagonist Cys2,Tyr3,Orn5,Pen7-amide blocked this response. The respective delta- and kappa-opioid receptor agonists, (D-Pen2, D-Pen5)-enkephalin and (+/-)-trans-U-50488 methanesulfonate had no effect. Voltage-clamp experiments showed that DAMGO activated an inwardly rectifying potassium conductance (GKIR) characterized by rectification at hyperpolarized potentials that increased in elevated extracellular potassium concentrations, a complete block by Ba2+ (1 mM), and a voltage-dependent block by Cs+. The extent of mu-opioid inhibition in other thalamic nuclei was then investigated. Widespread inhibition similar to that seen in the centrolateral nucleus was observed in a number of sensory, motor, intralaminar, and midline nuclei. Our results suggest that the net action of opioids would depend on their source: exogenous (systemically administered) opiates inhibiting the entire thalamus and favoring the shift of cell firing from tonic to bursting mode; and endogenously released opioids acting on specific thalamic nuclei, their release depending on the origin of the presynaptic input.
Brunton
J
J
Department of Physiology, University Medical Center, 1211 Geneva 4, Switzerland.
Charpak
S
S
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000187:drug effects*; D013787:Thalamic Nuclei / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D004745:Enkephalins; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D011188:Potassium